Alternate routes to the cell surface underpin insulin-regulated membrane trafficking of GLUT4

Kioumourtzoglou, D., Pryor, P. R., Gould, G. W. and Bryant, N. J. (2015) Alternate routes to the cell surface underpin insulin-regulated membrane trafficking of GLUT4. Journal of Cell Science, 128, pp. 2423-2429. (doi:10.1242/jcs.166561) (PMID:26071524) (PMCID:PMC4510850)

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Publisher's URL: http://jcs.biologists.org/content/early/2015/06/11/jcs.166561

Abstract

Insulin-stimulated delivery of glucose transporters (GLUT4) from specialized intracellular GLUT4 storage vesicles (GSVs) to the surface of fat and muscle cells is central to whole-body glucose. This translocation and subsequent internalization of GLUT4 back into intracellular stores transits numerous small membrane-bound compartments (internal GLUT4-containing vesicles; IGVs) including GSVs, but the function of these different compartments is not clear. Cellugyrin and sortilin define distinct populations of IGV; sortilin-positive IGVs represent GSVs, but the function of cellugyrin-containing IGVs is unknown. Here we demonstrate a role for cellugyrin in intracellular sequestration of GLUT4 in HeLa cells and have used a proximity ligation assay to follow changes in pairwise associations between cellugyrin, sortilin, GLUT4 and membrane trafficking machinery following insulin-stimulation of 3T3-L1 adipoctyes. Our data suggest that insulin stimulates traffic from cellugyrin- to sortilin- membranes, and that cellugyrin-IGVs provide an insulin-sensitive reservoir to replenish GSVs following insulin-stimulated exocytosis of GLUT4. Furthermore, our data support the existence of a pathway from cellugyrin-membranes to the surface of 3T3-L1 adipocytes that bypasses GSVs under basal conditions, and that insulin diverts traffic away from this into GSVs.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kioumourtzoglou, Mr Dimitrios and Gould, Professor Gwyn and Bryant, Dr Nia
Authors: Kioumourtzoglou, D., Pryor, P. R., Gould, G. W., and Bryant, N. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Journal of Cell Science
Publisher:The Company of Biologists Ltd.
ISSN:0021-9533
ISSN (Online):0021-9533
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Journal of Cell Science 128:2423-2429
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
500151Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES
500152Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES
580731How does tyrosine phosphorylation of SNARE proteins control GLUT4 vesicle fusion with the plasma membrane?Gwyn GouldDiabetes UK (DIABETESUK)11/0004289RI MOLECULAR CELL & SYSTEMS BIOLOGY